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What is azoospermia and can a person with azoospermia have biological children?

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Azoospermia is the term used when there is a complete absence of sperm in the ejaculate. Most patients assume that this diagnosis would rule out the possibility of his ever conceiving a child; if there are no sperm how can there be conception? However the reality is that a semen analysis which shows the absence of sperm in the ejaculate does not rule out either the possibility that sperm is being produced and not delivered to the semen, or that interventions may help the man produce sperm. Even in those cases where after intervention there is still no sperm in the ejaculate, there may be a possibility of harvesting small amounts of sperm, which have been produced in the testes as a result of the interventions.

A Production Problem or a Delivery Problem?

The primary question, which needs to be answered when faced with azoospermia, is whether the problem lies in the sperm production or in the delivery. That is, are the testes simply not producing sperm or are they producing sperm but unable to deliver it in the ejaculate? The purpose of an initial evaluation is to distinguish between these two alternatives. If the testes are making sperm but none are in the ejaculate, the sperm must be retrieved by some other mechanism, either by restoring the normal flow of sperm or by circumventing it. If the testes are not producing sperm then we need to explore whether the problem can be reversed. Even if the problem cannot be reversed, there are a number of cases in which the level of spermatogenesis is advanced enough to allow sperm "harvesting" in conjunction with advanced reproductive techniques (ART) and micromanipulation. The following paragraphs briefly describe causes for both production and delivery problems.

Production Problems

The three major causes for lack of sperm production are hormonal problems, "testicular failure," and varicocele.

Hormonal Problems: The testicles need pituitary hormones to be stimulated to make sperm. If these are absent or severely decreased, the testes will not maximally produce sperm. Importantly, men who take androgens (steroids) either by mouth or injection for body building shut down the production of hormones for sperm production.

Testicular Failure: This generally refers to the inability of the sperm producing part of the testicle (the seminiferous epithelium) to make adequate numbers of mature sperm. This failure may occur at any stage in sperm production for a number of reasons. Either the testicle may completely lack the cells that divide to become sperm (this is called "Sertoli cell-only syndrome.") or there may be an inability of the sperm to complete their development (this is termed a "maturation arrest.") This situation may be caused by genetic abnormalities, which must be screened for.

Varicocele: A varicocele is dilated veins in the scrotum, (just as an individual may have vericose veins in their legs.) These veins are dilated because the blood does not drain properly from them. These dilated veins allow extra blood to pool in the scrotum, which has a negative effect on sperm production. This condition may be corrected by minor out-patient surgery.

Sperm Delivery Problems - Ductal Absence or Blockage

Sperm delivery complications are generally caused either by a problem with the ductal system that carries the sperm, or problems with ejaculation. The sperm carrying ducts may be missing or blocked. Thus the patient may have bilateral (both sides) congenital (from birth) absence of the vas deferens. Or he may have obstructions either at the level of the epididymis (the delicate tubular structure draining the testes) or higher up in the more muscular vas deferens. He may have become mechanically blocked during hernia or hydrocele repairs.

Sperm are stored in sacs called the seminal vesicles, and then are deposited in the urethra, which is the tube through which men urinate and ejaculate. The sperm must pass through the ejaculatory ducts to get from the seminal vesicles to the urethra. If these are blocked on both sides no sperm will come through.

Finally, there may be problems with ejaculation. Before a man ejaculates, the sperm must first be deposited in the urethra. This process is called emission. There may be neurological damage from surgery, diabetes, or spinal cord injury, which prevents this from happening. Also, for the sperm to be pushed out the tip of the penis, the entry to the bladder must be closed down. If it does not close down the sperm will be pushed into the bladder, and later washed out when the patient urinates.

Evaluation of Azoospermia

Determining which of the above causes, or a combination of them, is the reason for the patient's azoospermia is often complex. Following is a brief discussion of some of the available tests and how they help in determining the cause.

Physical Examination

The simplest test is the physical exam. Since the bulk of the testes is comprised of the sperm producing elements, (the seminiferous epithelium), if the size of the testicles is severely diminished, this is an indication that the seminiferous epithelium is affected. Follow up hormonal profiles can determine whether this is a primary problem or caused by inadequate hormonal stimulation.

The scrotum is examined for the presence of dilated veins (varicocele). Their presence can be confirmed by an ultrasound probe placed on the skin at the scrotum.

During a physical exam, the ductal systems can be felt. If they are absent, the patient has what is called congenital bilateral absence of the vas deferens, (CBAVD). In most cases this is considered to be due to the patient's genetic make-up and requires chromosomal analysis as part of the evaluation and treatment.

Finally, during examination of the ductal structures, the epididymis may feel as though it is dilated. Generally, it is flat and the middle cannot be felt. Thus, a dilated epididymis may be indicative of a blockage.

Hormonal Evaluation

Follicle stimulating hormone (FSH) is the hormone made by the pituitary, which is responsible for stimulating the testes to make sperm. When the sperm producing capacity of the testes is diminished, the pituitary makes more FSH in an attempt to make the testes do its job. Therefore, if a man's FSH is significantly elevated there is a strong indication that his testicles are not producing sperm optimally. (Testosterone polactin, leutenizing hormone (LH) and thyroid stimulating hormone (TSH) are also measured to assess a man's hormonal status. These may reveal problems that can significantly impact sperm production).

Genetic Testing: This is an area of active research. At this point it is recommended that all men receive basic genetic testing, measuring the number of chromosomes and looking at the blocks of genetic material. Screening for the genes that can cause cystic fibrosis is sometimes suggested. There are tests for specific genetic abnormalities on the male chromosomes that can cause azoospermia. If a son were to inherit this, he may have the same problem.

Transrectal Ultrasound

In order to rule out a blockage of the ejaculatory duct, an ultrasound of the ejaculatory duct and seminal vesicles is often. performed. In this test the ultrasound probe is placed in the rectum since the ducts lie near its wall. Also, the ejaculatory duct traverses the prostate, a gland which can be felt through a man's rectal wall. If the seminal vesicles are dilated, this indicates that they may be full of semen because they cannot empty properly. Cysts blocking the ejaculatory ducts by exerting pressure on their walls, or calcifications in the ejaculatory ducts themselves, may also be noted. A cyst in some cases may be unroofed by operating through the urethra to open it thus decompressing the ejaculatory duct. If the blockage occurs within the ejaculatory duct, the blocked part may be removed in a similar operation.

Urinalysis

It is possible that ejaculation is occurring "backwards;" the sperm is being pushed into the bladder, and then washed out when the man urinates after ejaculation. To test for this we have the patient empty his bladder, and then ejaculate into a cup. He is then asked to urinate again into a different specimen container. If there are sperm in his urine, he has ejaculated backwards. Sometimes this can be corrected by oral medication. If not, the urine can be prepared so that it does not damage the sperm as much, and the sperm is then harvested from the post-ejaculatory urine.

Testicular Biopsy

Finally, if a primary testicular problem is suspected we can perform a testicular biopsy. A biopsy simply means obtaining actual tissue for laboratory/microscopic examination. This may be done using a needle through the skin, or by an incision.

In the past, indications for testicular biopsy were few. Through a combination of some tests outlined previously the problem could often be pinpointed as a primary testicular problem which had no treatment. It did not matter if a biopsy could identify whether the patient had absolutely no sperm production versus very low production because no treatment was available for either. However, recently that has changed as testicular sperm have been used to achieve pregnancies when coupled with in vitro fertilization (IVF) combined with intracytoplasmic sperm insertion (ICSI). In this procedure the sperm is harvested and then injected directly into the egg).

Conclusion

Most men facing a semen analysis fear the diagnosis of azoospermia. However, that diagnosis does not necessarily mean that the man produces no sperm or can never be made to produce any sperm and thus will never have a biological child. Accurate diagnosis of azoospermia is complicated. Correctible causes must be found and treated. Even then if there are no sperm in the ejaculate, sperm can often be harvested and used to achieve fertilization.
 


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